As a method for separating and collecting gamma-globulin from human blood, the method of Cohn, et al. has been habitually utilized (refer to Cohn, E. J., et al., J. Am. Chem. Soc., 68, 459-475 (1946) and ibid., 72, 465-474 (1950)). However, since the gamma-globulin obtained by the Cohn, et al. contains impurities which show a high anticomplementary activity, its use has been confined only to intramuscular injection. Even in the case of intramuscular injection, the above-mentioned gamma-globulin gives a topical pain, and moreover, since the gamma-globulin remains at the site of injection for a long time, satisfactorily high levels of gamma-globulin in the object's blood are not attainable due to the degradation of gamma-globulin during the long retention at the site of injection. Accordingly, in order to improve such a defect, a method for obtaining gamma-globulin for use safely in intravenous administration, for instance, methods of treating gamma-globulin with an enzyme and an acid, respectively and a method of chemically modifying gamma-globulin, has been devised.
However, owing to the several defects caused by these treatments such as the reduction of half-life of gamma-globulin and the problem of new antigenicity caused by these treatments, the production of a gamma-globulin with its original and native form as derived from human blood has attracted the attention.
As such a method, for instance, a method of using a copolymer of ethylene oxide and propylene glycol (Japanese Patent Application Laying Open No. 81519/74), a method of using hydroxyethylstarch and polyethylene glycol (Japanese Pat. No. 12001/80), a method of using polyethylene glycol (U.S. Pat. No. 4,165,370 and U.S. Pat. No. 4,124,576), etc. have been known.
Since it is very difficult to remove the high polymeric substance which has been once used to remove the impurities from the gamma-globulin and has remained together with the purified gamma-globulin, the high polymeric substance used in the process of the treatment of gamma-globulin is preferably removable completely from the purified gamma-globulin or is preferably administrable intravenously. However, the high polymeric substance which is in used according to the publicly known methods does not necessarily satisfy the above-mentioned conditions.
Further, the gamma-globulin purified by the above-mentioned method, in the case where it is formulated to be a pharmaceutical preparation by the usual method, shows its raised anticomplementary activity again. Accordingly, it is necessary to device a stabilizing method which inhibits the raise of the anticomplementary activity. As a method for stabilizing the purified gamma-globulin, a method of adding an amino acid, a sugar, a neutral salt or a high polymeric non-ionic surfactant of molecular weight of 2,000 to 20,000 at a relatively high concentration to gamma-globulin (Japanese Patent Applications Laying Open Nos. 47515/78 and 20124/79) and a method of adding a neutral salt such as sodium chloride and human serum albumin to gamma-globulin (Japanese Patent Application Laying Open No. 23115/79) are known. In the former case, owing to the high concentration of the stabilizing agent, the formulated preparation results in hypertonic, and in addition, among such additives there are substances not preferable for living bodies. On the other hand, in the latter case, even if the thus obtained purified gamma-globulin has almost no fear of causing transmission of serum hepatitis, however, human serum albumin is highly dangerous in causing such a disease, and the use of such a dangerous stabilizing agent should be avoided. The stability of the added human serum albumin itself also becomes a problem.